Iron-overload cardiomyopathy is prevalent on a worldwide basis and is a major co-morbidity in patients with genetic hemochromatosis and secondary iron overload. Therapies are limited in part due to lack of a valid pre-clinical model, which recapitulates advanced iron-overload cardiomyopathy. Male hemojuvelin knockout (HJVKO) mice, which lack hemojuvelin (HJV), a bone morphogenetic co-receptor protein required for hepcidin expression and systemic iron homeostasis, were fed a high iron diet starting at 4 weeks of age for a duration of 1 year...

Adult survivors of very preterm birth (≤32 weeks gestational age) without (PRE) and with bronchopulmonary dysplasia (BPD) have obstructive lung disease as evidenced by reduced expiratory airflow at rest and have significant mechanical ventilatory constraints during exercise. Airflow obstruction, under any condition, could be due to several factors including small airways. PRE and/or BPD could have smaller airways than their counterparts born at full-term (CON) due to a greater degree of dysanaptic airway development during the pre- and/or post-natal period...

BACKGROUND: In patients with bronchial obstruction estimating the location of the maximal obstruction is crucial for guiding interventional bronchoscopy. However, flow-volume curves cannot discriminate between the right and left lungs. OBJECTIVES: The aim of this study was to physiologically evaluate bronchial obstruction during interventional bronchoscopy. METHODS: We prospectively measured lateral airway pressure (Plat) at either side of the obstruction using a double-lumen catheter (pressure-pressure [P-P] curve) simultaneously to assess the degree of bronchial obstruction in 22 patients...

OBJECTIVE: To test the hypothesis that a simulation algorithm populated with data readily available from hemodynamic monitors and echocardiography can accurately model cardiac contractility, diastolic capacitance, and energetics. DESIGN: Bland-Altman analysis of paired data sets. SETTING: University laboratory. PARTICIPANTS: Archived data previously recorded from 7 anesthetized swine. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure and volume (LVV) data that had been continuously recorded over a range of inotropic conditions were used as reference data...

BACKGROUND: Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs) have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD...

Although detailed cell-based descriptors of cross-bridge cycling have been applied in finite element (FE) heart models to describe ventricular mechanics, these multiscale models have never been tested rigorously to determine if these descriptors, when scaled up to the organ-level, are able to reproduce well-established organ-level physiological behaviors. To address this void, we here validate a left ventricular (LV) FE model that is driven by a cell-based cross-bridge cycling descriptor against key organ-level heart physiology...

This paper presents an oscillometric blood pressure (BP) measurement approach based on the active control schemes of cuff pressure. Compared with conventional electronic BP instruments, the novelty of the proposed BP measurement approach is to utilize a variable volume chamber which actively and stably alters the cuff pressure during inflating or deflating cycles. The variable volume chamber is operated with a closed-loop pressure control scheme, and it is activated by controlling the piston position of a single-acting cylinder driven by a screw motor...

β-Lactoglobulin, being one of the principal whey protein, is of huge importance to the food industry. Temperature/pressure effects on this small protein has been extensively studied by industry. To characterize biochemical properties of β-lactoglobulin after or during pressurization, a wide range of methods have been used thus far. In this study, for the first time, the pressure-induced conformation of β-lactoglobulin in the crystal state was determined, at pressure 430 MPa. Changes observed in the high pressure structure correlate with the physico-chemical properties of pressure-treated β-lactoglobulin obtained from dynamic light scattering, electrophoretic mobility and quartz crystal microbalance with dissipation monitoring measurements...

BACKGROUND: The purpose of this study was to investigate the associations between clinical factors and cardiac function as measured by pressure-volume loops (PVLs) in a pediatric heart transplant cohort. METHODS: Patients (age < 20 years) who underwent heart transplantation presenting for a clinically indicated catheterization were enrolled. PVLs were recorded using microconductance catheters (CD Leycom(®), Zoetermeer, Netherlands). Demographic data, serum B-type natriuretic peptide (BNP), time from transplant, ischemic time, presence of transplant coronary artery disease, donor-specific antibodies, and history of rejection were recorded at the time of catheterization...

BACKGROUND: Understanding the effects of cardiac diseases on the heart's functionality which is the purpose of many biomedical researches, directly affects the diagnostic and therapeutic methods. Myocardial infarction (MI) is a common complication of cardiac ischemia, however, the impact of MI on the left ventricle (LV) flow patterns has not been widely considered by computational fluid dynamics studies thus far. METHODS: In this study, we present an insightful numerical method that creates an artificial MI on an image-based fluid-structure interactional model of normal LV to investigate its influence on the flow in comparison with the normal case...

The use of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) to support patients with acute heart failure has been associated with ventricular distension and pulmonary edema, the mechanism of which is not fully understood. This study examined the impact of VA ECMO on left ventricular (LV) Starling curves to elaborate a framework for anticipating and treating LV distension. A previously developed and validated model of the cardiovascular system was used to generate pressure-volume (PV) loops and Starling curves while holding mean arterial pressure (mABP) constant at a range of values either by adjusting systemic resistance or by adding VA ECMO support...

This paper develops a method for the minimally invasive, beat-by-beat estimation of the left ventricular pressure-volume loop. This method estimates the left ventricular pressure and volume waveforms that make up the pressure-volume loop using clinically available inputs supported by a short, baseline echocardiography reading. Validation was performed across 142,169 heartbeats of data from 11 Piétrain pigs subject to two distinct protocols encompassing sepsis, dobutamine administration and clinical interventions...

The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl-]i and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity as STK39, the gene encoding SPAK has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T-loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored...

BACKGROUND: Hemodynamic resuscitation in septic shock requires aggressive fluid replacement and appropriate use of vasopressors to optimize arterial pressure (AP) and cardiac output (CO). Because responses to these drugs vary between patients and within patient over time, strict monitoring of patient condition and repetitive adjustment of drug dose are required. This task is time and labor consuming, and is associated with poor adherence to resuscitation guidelines. To overcome this issue, we developed a computer-controlled closed-loop drug infusion system for automated hemodynamic resuscitation in septic shock, and evaluated the performance of the system in a canine model of endotoxin shock...

We present a fully-coupled fluid-electromechanics model of the heart using a generic biventricular structure to provide a tool for future multiphysics interaction studies. A simplified Purkinje fibre structure was embedded within the myocardium along with transmural variation of action potential duration to obtain realistic activation and relaxation sequences. To ease computational requirements, phenomenological action potential and excitation-contraction formulations were chosen, and coupled to transverse isotropic hyperelastic myocardial material physics...

In the development of a left ventricular assist device (LVAD), it is important to evaluate the LVAD's hemodynamic effect on the compromised left ventricle (LV) before surgical implantation. The mock circulatory loop (MCL) is widely accepted as an in vitro test platform to evaluate LVADs across a wide range of operational conditions as a way to examine how the device and the cardiovascular system interact. Unfortunately, most MCLs represent an oversimplified model of cardiac function, with disease states simulated through generalized changes in heart rate and stroke volume...

BACKGROUND: Mechanical right ventricular (RV) support in pulmonary arterial hypertension patients has been feared to cause pulmonary hemorrhage and to be detrimental for the after-load-sensitive RV. Continuous low-flow pumps offer promise but remain insufficiently tested. METHODS: The pulmonary artery was banded in 20 sheep in this study. Eight weeks later, a Synergy micro-pump (HeartWare International, Framingham MA) was inserted in 10 animals, driving blood from the right atrium to the pulmonary artery...

AIMS: Guidelines advocate down-titration of loop diuretics in chronic heart failure (CHF) when patients have no signs of volume overload. Limited data are available on the expected success rate of this practice or how routine diagnostic tests might help steering this process. METHODS AND RESULTS: Fifty ambulatory CHF-patients on stable neurohumoral blocker/diuretic therapy for at least 3months without any clinical sign of volume overload were prospectively included to undergo loop diuretic down-titration...

Aims: The relationship between echocardiographic measures of left ventricular (LV) systolic function and reference-standard measures have not been assessed in children. The objective of this study was to assess the validity of echocardiographic indices of LV systolic function via direct comparison to a novel composite measure of contractility derived from pressure-volume loop (PVL) analysis. Methods and results: Children with normal loading conditions undergoing routine left heart catheterization were prospectively enrolled...